The research program consists of the development of cytochemical methods for light and electron microscopy and the design and synthesis of new possible chemotherapeutic agents. The latter agents are studied in animals and if appropriate, in patients with advanced cancer. We are now determining the structural requirements for making substrates specific for prostatic acid phosphatase as compared to other acid phosphatases and alkaline phosphatses. These features will be incorporated into phosphate esters that will yield cytotoxic agents after hydrolysis by prostatic acid phosphatase. Their effects on normal animal prostatic epithelium will be studied first and if damage is sufficiently confined to these cells, the agents will be studied in patients with prostatic carcinoma. In cytochemistry we are working on methods for the ultrastructural demonstration of monoamine oxidase, photoreduction of chloroplasts, improved methods for the dehydrogenases and oxidases including cytochrome p-450 and hydrolytic enzymes. Our methods will yield lipophobic or polymeric water-insoluble, osmiophilic end-products so that membrane bound enzymes will be accurately localized.